Influence of Subclinical Atherosclerosis Burden and Progression on Mortality.

BACKGROUND: Atherosclerosis is a dynamic process. There is little evidence regarding whether quantification of atherosclerosis extent and progression, particularly in the carotid artery, in asymptomatic individuals predicts all-cause mortality. OBJECTIVES: This study sought to evaluate the independent predictive value (beyond cardiovascular risk factors) of subclinical atherosclerosis burden and progression and all-cause mortality. METHODS: A population of 5,716 asymptomatic U.S. adults (mean age 68.9 years, 56.7% female) enrolled between 2008 and 2009 in the BioImage (A Clinical Study of Burden of Atherosclerotic Disease in an At Risk Population) study underwent examination by vascular ultrasound to quantify carotid plaque burden (cPB) (the sum of right and left carotid plaque areas) and by computed tomography for coronary artery calcium (CAC). Follow-up carotid vascular ultrasound was performed on 732 participants a median of 8.9 years after the baseline exam. All participants were followed up for all-cause mortality, the primary outcome. Trend HRs are the per-tertile increase in each variable. RESULTS: Over a median 12.4 years' follow-up, 901 (16%) participants died. After adjustment for cardiovascular risk factors and background medication, baseline cPB and CAC score were both significantly associated with all-cause mortality (fully adjusted trend HR: 1.23; 95% CI: 1.16-1.32; and HR: 1.15; 95% CI: 1.08-1.23), respectively (both P < 0.001), thus providing additional prognostic value. cPB performed better than CAC score. In participants with a second vascular ultrasound evaluation, median cPB progressed from 29.2 to 91.3 mm3. cPB progression was significantly associated with all-cause mortality after adjusting for cardiovascular risk factors and baseline cPB (HR: 1.03; 95% CI: 1.01-1.04 per absolute 10-mm3 change; P = 0.01). CONCLUSIONS: Subclinical atherosclerosis burden (cPB and CAC) in asymptomatic individuals was independently associated with all-cause mortality. Moreover, atherosclerosis progression was independently associated with all-cause mortality.

Feedback modulation of Orai1α and Orai1ß protein content mediated by STIM proteins.

Store-operated Ca2+ entry is a mechanism controlled by the filling state of the intracellular Ca2+ stores, predominantly the endoplasmic reticulum (ER), where ER-resident proteins STIM1 and STIM2 orchestrate the activation of Orai channels in the plasma membrane, and Orai1 playing a predominant role. Two forms of Orai1, Orai1α and Orai1ß, have been identified, which arises the question whether they are equally regulated by STIM proteins. We demonstrate that STIM1 preferentially activates Orai1α over STIM2, yet both STIM proteins similarly activate Orai1ß. Under resting conditions, there is a pronounced association between STIM2 and Orai1α. STIM1 and STIM2 are also shown to influence the protein levels of the Orai1 variants, independently of Ca2+ influx, via lysosomal degradation. Interestingly, Orai1α and Orai1ß appear to selectively regulate the protein level of STIM1, but not STIM2. These observations offer crucial insights into the regulatory dynamics between STIM proteins and Orai1 variants, enhancing our understanding of the intricate processes that fine-tune intracellular Ca2+ signaling.

Intestinal microbiome as a diagnostic marker of coronary artery disease: a systematic review and meta-analysis.

Background: The intestinal microbiome has been recently linked to several metabolic and chronic disorders, one of which is coronary artery disease (CAD). Our study aimed to analyze the intestinal microbiome of CAD patients and assess the eligibility of dysbiosis as a diagnostic marker of CAD. Methods: PubMed, Scopus, Embase, and Web of Science were searched using terms, such as 'CAD' and 'microbiome'. Only observational controlled studies were included. R version 4.2.2 was used for the analysis. Results: A significant association was found between the CAD group and increased Simpson and Shannon Indices compared with the control group (MD=0.04, 95% CI=0.03-0.05, and MD=0.11, 95% CI=0.01-0.22, respectively). Our analysis yielded a statistically significant association between the CAD group and increased Prevotella genus (MD=13.27, 95% CI=4.12-22.42, P-value=0.004), Catenibacterium genus (MD=0.09, 95% CI=0.09-0.10), Pseudomonas genus (MD=0.54, 95% CI=0.29-0.78, P-value), and Subdoligranulum (MD=-0.06, 95% CI=-0.06 to -0.06) compared with the control group. Another significant association was detected between the CAD group and decreased Bacteroides vulgatus and Bacteroides dorei (MD=-10.31, 95% CI=-14.78 to -5.84, P-value <0.00001). Conclusion: Dysbiosis is an acceptable diagnostic marker of CAD. Decreased B. dorei and B. vulgatus among CAD patients suggests a protective role of these bacteria. Future clinical trials are necessary to investigate the potential benefit of supplementation of these bacteria in treating or preventing CAD.

Commentary: A road map for future data-driven urban planning and environmental health research.

Recent advances in data science and urban environmental health research utilise large-scale databases (100s-1000s of cities) to explore the complex interplay of urban characteristics such as city form and size, climate, mobility, exposure, and environmental health impacts. Cities are still hotspots of air pollution and noise, suffer urban heat island effects and lack of green space, which leads to disease and mortality burdens preventable with better knowledge. Better understanding through harmonising and analysing data in large numbers of cities is essential to identifying the most effective means of disease prevention and understanding context dependencies important for policy.

Contribution of extracellular vesicles to steatosis-related liver disease and their therapeutic potential.

Extracellular vesicles (EVs) are small particles released by many cell types in different tissues, including the liver, and transfer specific cargo molecules from originating cells to receptor cells. This process generally culminates in activation of distant cells and inflammation and progression of certain diseases. The global chronic liver disease (CLD) epidemic is estimated at 1.5 billion patients worldwide. Cirrhosis and liver cancer are the most common risk factors for CLD. However, hepatitis C and B virus infection and obesity are also highly associated with CLD. Nonetheless, the etiology of many CLD pathophysiological, cellular, and molecular events are unclear. Changes in hepatic lipid metabolism can lead to lipotoxicity events that induce EV release. Here, we aimed to present an overview of EV features, from definition to types and biogenesis, with particular focus on the molecules related to steatosis-related liver disease, diagnosis, and therapy.

Minimally Invasive Assessment of Peripheral Residual Disease During Maintenance or Observation in Transplant-Eligible Patients With Multiple Myeloma.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.

Fluorination of antimonene hexagons.

Fluorination of two-dimensional (2D) antimonene hexagons synthesized through a colloidal bottom-up approach has been explored using microwave-induced plasma and reactive ion etching fluorination strategies through the generation of CF4. The stability of the fluorine bond has been corroborated through DFT calculations. This work paves the way for further halogen-derivative modifications of heavy 2D pnictogens.

Impact of high-risk and low-risk human papillomavirus infections on the male genital tract: effects on semen inflammation and sperm quality.

Human Papillomavirus (HPV), a prevalent sexually transmitted infection, comprises high-risk (HR-HPV) and low-risk (LR-HPV) viruses, the former posing a high risk for developing malignancies whereas the latter mainly for benign warts. Despite increasing awareness of HPV's impact on men's health, the influence of HR-HPV and LR-HPV urogenital infections on male fertility potential remains uncertain. This study aimed to investigate whether male urogenital infection with HR- or LR-HPV associates with impaired sperm quality, oxidative stress, and inflammation. A total of 205 male patients attending an urology clinic were enrolled. Semen samples were analyzed for HPV using PCR and genotyped by RFLP. Semen quality was evaluated following WHO guidelines. Semen leukocytes, reactive oxygen species (ROS), and sperm viability were analyzed using flow cytometry. HPV was detected in 19% (39/205) of semen samples. HR-HPV infections were more prevalent, with HPV-16 being the most frequent genotype. Neither HR-HPV nor LR-HPV were associated with significant alterations in routine sperm quality parameters. However, HR-HPV+ individuals showed significantly higher levels of sperm necrosis and exhibited increased proportions of ROS+ spermatozoa compared to LR-HPV+ or control individuals. Furthermore, no significant semen inflammation was detected in patients infected with either HR-HPV or LR-HPV, and unexpectedly reduced semen leukocytes and inflammatory cytokines (IL-6 and IL-1ß) were observed in HR-HPV+ patients compared to controls. These observations underscore the importance of comprehensive HPV screening, including genotyping, in urology and fertility clinics to understand the progression of the infection, potential adverse effects on reproductive health, and the oncogenic risks involved.

Tunable SIM properties in a family of 3D anilato-based lanthanide-MOFs.

By reacting a 3,6-ditriazolyl-2,5-dihydroxybenzoquinone (H2trz2An) anilato linker with LnIII ions (LnIII = Dy, Tb, Ho), two different series of polymorphs, formulated as [Ln2(trz2An)3(H2O)4] n ·10H2O (DyIII, 1a; TbIII, 2a, HoIII, 3a) and [Ln2(trz2An)3(H2O)4] n ·7H2O (DyIII, 1b, TbIII, 2b, HoIII, 3b) have been obtained. In these series the two DyIII-coordination networks (1a and 1b) and the TbIII-coordination polymer (2b) show a Single Ion Magnet (SIM) behavior. 1-3a MOFs show reversible structural flexibility upon removal of a coordinated water molecule from a distorted hexagonal 2D framework to a distorted 3,6-brickwall rectangular 3D structure in [Ln2(trz2An)3(H2O)2] n ·2H2O (DyIII, 1a_des; TbIII, 2a_des, HoIII, 3a_des) involving shrinkage/expansion of the hexagonal-rectangular networks. Noteworthy, 2b represents the first example of a TbIII-anilate-based coordination polymer showing SIM behaviour to date and the best SIM properties within the polymorphs. Theoretical investigation via ab initio CASSCF calculations supports this behavior, since 2b shows less mixing between the m J states of the ground state among all the studied complexes.

Identification of PRMT5 as a therapeutic target in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified. OBJECTIVE: We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA. DESIGN: We evaluated the expression of PRMT5, its functional partner MEP50 and methylthioadenosine phosphorylase (MTAP)-an enzyme that modulates the sensitivity of PRMT5 to pharmacological inhibitors-in human CCA tissues. PRMT5-targeting drugs, currently tested in clinical trials for other malignancies, were assessed in human CCA cell lines and organoids, as well as in two immunocompetent CCA mouse models. Transcriptomic, proteomic and functional analyses were performed to explore the underlying antitumoural mechanisms. RESULTS: PRMT5 and MEP50 proteins were correlatively overexpressed in most CCA tissues. MTAP was absent in 25% of intrahepatic CCA. PRMT5-targeting drugs markedly inhibited CCA cell proliferation, synergising with cisplatin and gemcitabine and hindered the growth of cholangiocarcinoma organoids. PRMT5 inhibition blunted the expression of oncogenic genes involved in chromatin remodelling and DNA repair, consistently inducing the formation of RNA loops and promoting DNA damage. Treatment with PRMT5-targeting drugs significantly restrained the growth of experimental CCA without adverse effects and concomitantly induced the recruitment of CD4 and CD8 T cells to shrinking tumourous lesions. CONCLUSION: PRMT5 and MEP50 are frequently upregulated in human CCA, and PRMT5-targeting drugs have significant antitumoural efficacy in clinically relevant CCA models. Our findings support the evaluation of PRMT5 inhibitors in clinical trials, including their combination with cytotoxic and immune therapies.

Intercostal Lung Hernias Presenting After Minimally Invasive Cardiac Surgery.

INTRODUCTION: With the introduction of minimally invasive cardiac surgery, more commonly cases of lung herniation are starting to appear. Acquired lung hernias are classified as postoperative, traumatic, pathologic, and spontaneous. Up to 83% of lung hernias are intercostal. Herein, we describe patients presenting with intercostal lung hernias following minimally invasive cardiac surgery at a single center in Medellín, Colombia. METHODS: We conducted a retrospective search of all patients presenting with intercostal lung hernias secondary to minimally invasive cardiac surgery at our clinic in Medellín since the beginning of our program, from 2010 to 2022. Mini-sternotomies were excluded from our study. We reviewed the incision type and other possible factors leading to intercostal lung hernia development. We also describe the approach taken for these patients. RESULTS: From 2010 up until 2022, 803 adult patients underwent minimally invasive cardiac surgeries through a mini-thoracotomy. At the time of data retrieval, nine patients presented with intercostal lung hernias at the previous incision site. Five hernias (55%) were from right 2nd intercostal parasternal mini-thoracotomies for aortic valve surgeries. Four hernias (45%) were from right 4th intercostal lateral mini-thoracotomies for mitral valve surgeries. Our preferred repair technique is a video-assisted thoracoscopic mesh approach. CONCLUSION: Minimally invasive cardiac surgical approaches are becoming more routine. Proper wound closure is critical in preventing lung hernias. Additionally, timely diagnosis and opportune hernia surgery using video-assisted thoracoscopic mesh repair can prevent further complications.

Anelosimuseximius bioinspired ZnO nano cobwebs for environmental remediation of drugs and endocrine disruptors from water.

The pollution of wastewater with pharmaceuticals and endocrine-disrupting chemicals (EDCs) in populated areas poses a growing threat to humans and ecosystems. To address this serious problem, various one-dimensional (1D) hierarchical ZnO-based nanostructures inspired by Anelosimus eximius cobwebs were developed and successfully grown on a glass substrate through simple hydrothermal synthesis. The nanorods (nr) obtained during primary growth were chemically etched with KOH (ZnOnr-KOH), followed by the secondary growth of nano cobweb-like (ncw) structures using polyethyleneimine (ZnOnr/ncw). These structures were further decorated by the photoreduction of Ag nanoparticles (ZnOnr/ncw/Ag). The feasibility of ZnO-based 1D nanostructures to remove pollutants was demonstrated by degrading commonly prescribed pharmaceutical drugs (diclofenac and carbamazepine) in a miniature cuvette reactor. The photocatalytic activities for drug degradation generally decreased in the order ZnOnr/ncw/Ag > ZnOnr/ncw > ZnOnr-KOH. Additionally, the suitability of the samples for scaling up and practical application was demonstrated by photocatalytic degradation of the hormone estriol (E3) in a flow-through photoreactor. The photocatalytic degradation efficiency of E3 followed the same trend observed for drug degradation, with the complete elimination of the endocrine disruptor achieved by the best-performing ZnOnr/ncw/Ag within 4 h, due to optimized charge transfer and separation at the heterostructure interface.

Non-mitogenic FGF19 mRNA-based therapy for the treatment of experimental metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic dysfunction-associated steatohepatitis (MASH), represents a global health threat. MASH pathophysiology involves hepatic lipid accumulation and progression to severe conditions like cirrhosis and, eventually, hepatocellular carcinoma. Fibroblast growth factor (FGF)-19 has emerged as a key regulator of metabolism, offering potential therapeutic avenues for MASH and associated disorders. We evaluated the therapeutic potential of non-mitogenic (NM)-FGF19 mRNA formulated in liver-targeted lipid nanoparticles (NM-FGF19-mRNAs-LNPs) in C57BL/6NTac male mice with diet-induced obesity and MASH (DIO-MASH: 40% kcal fat, 20% kcal fructose, 2% cholesterol).  After feeding this diet for 21 weeks, NM-FGF19-mRNAs-LNPs or control (C-mRNA-LNPs) were administered (0.5 mg/kg, i.v.) weekly for another six weeks, in which diet feeding continued. NM-FGF19-mRNAs-LNPs treatment in DIO-MASH mice resulted in reduced body weight, adipose tissue depots, and serum transaminases, along with improved insulin sensitivity. Histological analyses confirmed the reversal of MASH features, including steatosis reduction without worsening fibrosis. NM-FGF19-mRNAs-LNPs reduced total hepatic bile acids (BA) and changed liver BA composition, markedly influencing cholesterol homeostasis and metabolic pathways as observed in transcriptomic analyses. Extrahepatic effects included the downregulation of metabolic dysfunction-associated genes in adipose tissue. This study highlights the potential of NM-FGF19-mRNA-LNPs therapy for MASH, addressing both hepatic and systemic metabolic dysregulation. NM-FGF19-mRNA demonstrates efficacy in reducing liver steatosis, improving metabolic parameters, and modulating BA levels and composition. Given the central role played by BA in dietary fat absorption, this effect of NM-FGF19-mRNA may be mechanistically relevant. Our study underscores the high translational potential of mRNA-based therapies in addressing the multifaceted landscape of MASH and associated metabolic perturbations.

Opening the Hysteresis Loop in Ferromagnetic Fe3GeTe2 Nanosheets Through Functionalization with TCNQ Molecules.

Ferromagnetic metal Fe3GeTe2 (FGT), whose structure exhibits weak van-der-Waals interactions between 5-atom thick layers, was subjected to liquid-phase exfoliation (LPE) in N-methyl pyrrolidone (NMP) to yield a suspension of nanosheets that were separated into several fractions by successive centrifugation at different speeds. Electron microscopy confirmed successful exfoliation of bulk FGT to nanosheets as thin as 6 nm. The ferromagnetic ordering temperature for the nanosheets gradually decreased with the increase in the centrifugation speed used to isolate the 2D material. These nanosheets were resuspended in NMP and treated with an organic acceptor, 7,7,8,8-tetracyano-quinodimethane (TCNQ), which led to precipitation of FGT-TCNQ composite. The formation of the composite material is accompanied by charge transfer from the FGT nanosheets to TCNQ molecules, generating TCNQ•- radical anions, as revealed by experimental vibrational spectra and supported by first principles calculations. Remarkably, a substantial increase in magnetic anisotropy was observed, as manifested by the increase in the coercive field from nearly zero in bulk FGT to 1.0 kOe in the exfoliated nanosheets and then to 5.4 kOe in the FGT-TCNQ composite. The dramatic increase in coercivity of the composite suggests that functionalization with redox-active molecules provides an appealing pathway to enhancing magnetic properties of 2D materials.

Sodium Bicarbonate In In-Hospital and Out-of-Hospital Cardiac Arrest: A Systematic Literature Review.

Cardiac arrest is a common cause of death worldwide. Sodium bicarbonate (SB) has commonly been used during cardiopulmonary resuscitation (CPR) to correct metabolic acidosis (MA). However, the existence of evidence about its administration remains controversial. This systematic review aimed to summarize the effectiveness of SB in patients with in-hospital and out-of-hospital cardiac arrest. We searched Medline, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies that used SB in cardiac arrest, from November 1962 until December 2023. A total of 372 records were identified and 12 studies were included. Despite few studies suggesting that SB may improve outcomes in prolonged CPR, the overall data revealed that SB was associated with lower rates of ROSC and outcomes. This review conceded that there is limited evidence to warrant the use of SB during CPR other than under specific conditions, which include hyperkalemic cardiac arrest, severe cardiotoxicity, or overdose due to tricyclic antidepressants. In conclusion, SB is not recommended for conventional use in patients with cardiac arrest. Further studies should be performed to determine whether it has any benefit in these scenarios.

Challenges Reconciling Theory and Experiments in the Prediction of Lattice Thermal Conductivity: The Case of Cu-Based Sulvanites.

The exploration of large chemical spaces in search of new thermoelectric materials requires the integration of experiments, theory, simulations, and data science. The development of high-throughput strategies that combine DFT calculations with machine learning has emerged as a powerful approach to discovering new materials. However, experimental validation is crucial to confirm the accuracy of these workflows. This validation becomes especially important in understanding the transport properties that govern the thermoelectric performance of materials since they are highly influenced by synthetic, processing, and operating conditions. In this work, we explore the thermal conductivity of Cu-based sulvanites by using a combination of theoretical and experimental methods. Previous discrepancies and significant variations in reported data for Cu3VS4 and Cu3VSe4 are explained using the Boltzmann Transport Equation for phonons and by synthesizing well-characterized defect-free samples. The use of machine learning approaches for extracting high-order force constants opens doors to charting the lattice thermal conductivity across the entire Cu-based sulvanite family-finding not only materials with κ l values below 2 W m-1 K-1 at moderate temperatures but also rationalizing their thermal transport properties based on chemical composition.

A New Real-Time Simple Method to Measure the Endogenous Nitrate Reductase Activity (Nar) in Paracoccus denitrificans and Other Denitrifying Bacteria.

The transmembrane nitrate reductase (Nar) is the first enzyme in the dissimilatory alternate anaerobic nitrate respiratory chain in denitrifying bacteria. To date, there has been no real-time method to determine its specific activity embedded in its native membrane; here, we describe such a new method, which is useful with the inside-out membranes of Paracoccus denitrificans and other denitrifying bacteria. This new method takes advantage of the native coupling of the endogenous NADH dehydrogenase or Complex I with the reduction of nitrate by Nar through the quinone pool of the inner membranes of P. denitrificans. This is achieved under previously reached anaerobic conditions. Inner controls confirming the specific Nar activity determined by this new method were made by the total inhibition of the Nar enzyme by sodium azide and cyanide, well-known Nar inhibitors. The estimation of the Michaelis-Menten affinity of Nar for NO3- using this so-called Nar-JJ assay gave a Km of 70.4 µM, similar to previously determined values. This new Nar-JJ assay is a suitable, low-cost, and reproducible method to determine in real-time the endogenous Nar activity not only in P. denitrificans, but in other denitrifying bacteria such as Brucella canis, and potentially in other entero-pathogenic bacteria.

Staurosporine as a Potential Treatment for Acanthamoeba Keratitis Using Mouse Cornea as an Ex Vivo Model.

Acanthamoeba is a ubiquitous genus of amoebae that can trigger a severe and progressive ocular disease known as Acanthamoeba Keratitis (AK). Furthermore, current treatment protocols are based on the combination of different compounds that are not fully effective. Therefore, an urgent need to find new compounds to treat Acanthamoeba infections is clear. In the present study, we evaluated staurosporine as a potential treatment for Acanthamoeba keratitis using mouse cornea as an ex vivo model, and a comparative proteomic analysis was conducted to elucidate a mechanism of action. The obtained results indicate that staurosporine altered the conformation of actin and tubulin in treated trophozoites of A. castellanii. In addition, proteomic analysis of treated trophozoites revealed that this molecule induced overexpression and a downregulation of proteins related to key functions for Acanthamoeba infection pathways. Additionally, the ex vivo assay used validated this model for the study of the pathogenesis and therapies of AK. Finally, staurosporine eliminated the entire amoebic population and prevented the adhesion and infection of amoebae to the epithelium of treated mouse corneas.

Saliva as a Potential Source of Biomarkers in Cows with Metritis: A Pilot Study.

Metritis affects 5-20% of cows after parturition, negatively impacting animal welfare and the profitability of dairy farms, increasing culling rates and costs, and decreasing productivity and reproduction rates. This study compared the results of a comprehensive biochemical panel consisting of 25 salivary and 31 serum analytes between healthy cows (n = 16) and cows with metritis (n = 12). Descriptive parameters such as depression, rectal temperature, body condition score (BCS), heart rate, respiratory rate, mucous color, ruminal motility, vaginal discharge, milk production, and complete hematology analyses were also assessed for comparative purposes. The biochemistry analytes comprised five analytes related to stress, five to inflammation, five to oxidative status, and nineteen to general metabolism. The two-way ANOVA analysis revealed that, in saliva, eight biomarkers (lipase, adenosine deaminase (ADA), haptoglobin (Hp), total proteins, g-glutamyl transferase (gGT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatine kinase (CK)) were significant higher in cows with metritis. In serum, eight biomarkers (ADA, Hp, serum amyloid A (SAA), fibrinogen, ferritin, AOPPs/albumin ratio, non-esterified fatty acids (NEFAs), and bilirubin) were significantly higher in cows with metritis, whereas six (total esterase (TEA), albumin, urea, lactate, phosphorus, and calcium) were lower. Of the total number of 23 biomarkers that were measured in both saliva and serum, significant positive correlations between the two biofluids were found for six of them (Hp, FRAP, CUPRAC, AOPPs, urea, and phosphorus). Urea showed an R = 0.7, and the correlations of the other analytes were weak (R < 0.4). In conclusion, cows with metritis exhibited differences in biomarkers of stress, inflammation, cellular immune system, and general metabolism in both salivary and serum biochemistry profiles. These changes were of different magnitudes in the two biofluids. In addition, with the exception of ADA and Hp, the analytes that showed changes in the saliva and serum profiles of cows affected by metritis were different. Overall, this report opens a new window for the use of saliva as potential source of biomarkers in cows with metritis.